Background: PraderWilli syndrome (PWS) results from abnormalities in the genomic imprinting process leading to hypothalamic dysfunction with an alteration of GH secretion. PWS is associated with early morbid obesity and short stature which can be efficiently improved with GH treatment.
Objective and hypotheses: Our aims were to highlight adipose tissue structural and functional impairments in young children with PWS and to study the effect of GH treatment.
Method: Adipose tissue (AT) biopsies were obtained during scheduled surgeries from control lean children (n=15, age=40.6±5.9 months), untreated lean PWS children (n=7, age=19.6±3.8 months) or PWS children under GH treatment for at least 1 year (n=8, age=103.6±20.1 months). This study is part of a prospective national multicenter study evaluating both in vivo and in vitro GH sensitivity in PWS approved by the Local Ethical Committee (no. EUDRACT 2008-004612-12).
Results: Analysis of biopsies revealed that in stromal vascular fraction of AT, adipose progenitor cells (CD34+/CD31−/CD14− cells) were significantly reduced in untreated PWS AT when compared to control samples (75 000 cells/g of control AT to 40 000 cells in the same amount of PWS tissue). GH treatment tended to restore this population of progenitor cells in AT. Isoprenaline strongly activated lipolysis in control adipocytes (maximal 12-fold increase of basal lipolysis) whereas this β-adrenergic agonist effect was partially lost in adipocytes from PWS children (maximum fourfold activation). In contrast, isoprenaline-induced stimulation over basal lipolysis was stronger in GH-treated than untreated PWS adipocytes.
Conclusion: Herein, we report adipose tissue dysfunctions in children with PWS which may be partially restored by GH treatment.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology